Improving power and accuracy of genome-wide association studies via a multi-locus mixed linear model methodology

Genome-wide association studies (GWAS) have been widely used in genetic dissection of complex traits. However, common methods are all based on a fixed-SNP-effect mixed linear model (MLM) and single marker analysis, such as efficient mixed model analysis (EMMA). These methods require Bonferroni correction for multiple tests, which often is too conservative when the number of markers is extremely large. To address this concern, we proposed a random-SNP-effect MLM (RMLM) and a multi-locus RMLM (MRMLM) for GWAS. The RMLM simply treats the SNP-effect as random, but it allows a modified Bonferroni correction to be used to calculate the threshold p value for significance tests. The MRMLM is a multi-locus model including markers selected from the RMLM method with a less stringent selection criterion. Due to the multi-locus nature, no multiple test correction is needed. Simulation studies show that the MRMLM is more powerful in QTN detection and more accurate in QTN effect estimation than the RMLM, which in turn is more powerful and accurate than the EMMA. To demonstrate the new methods, we analyzed six flowering time related traits in Arabidopsis thaliana and detected more genes than previous reported using the EMMA. Therefore, the MRMLM provides an alternative for multi-locus GWAS.

Evaluation of a modern-analogue methodology for reconstructing Australian palaeoclimate from pollen

Quantitative palaeoclimate reconstructions are widely used to evaluate climatemodel performance. Here, as part of an effort to provide such a data set for Australia, we examine the impact of analytical decisions and sampling assumptions on modern-analogue reconstructions using a continent-wide pollen data set. There is a high degree of correlation between temperature variables in the modern climate of Australia, but there is sufficient orthogonality in the variations of precipitation, summer and winter temperature and plant–available moisture to allow independent reconstructions of these four variables to be made. The method of analogue selection does not affect the reconstructions, although bootstrap resampling provides a more reliable technique for obtaining robust measures of uncertainty. The number of analogues used affects the quality of the reconstructions: the most robust reconstructions are obtained using 5 analogues. The quality of reconstructions based on post-1850 CE pollen samples differ little from those using samples from between 1450 and 1849 CE, showing that European post settlement modification of vegetation has no impact on the fidelity of the reconstructions although it substantially increases the availability of potential analogues. Reconstructions based on core top samples are more realistic than those using surface samples, but only using core top samples would substantially reduce the number of available analogues and therefore increases the uncertainty of the reconstructions. Spatial and/or temporal averaging of pollen assemblages prior to analysis negatively affects the subsequent reconstructions for some variables and increases the associated uncertainties. In addition, the quality of the reconstructions is affected by the degree of spatial smoothing of the original climate data, with the best reconstructions obtained using climate data froma 0.5° resolution grid, which corresponds to the typical size of the pollen catchment. This study provides a methodology that can be used to provide reliable palaeoclimate reconstructions for Australia, which will fill in a major gap in the data sets used to evaluate climate models.

Alan Rugman’s methodology

This paper argues that the intellectual contribution of Alan Rugman reflects his distinctive research methodology. Alan Rugman trained as an economist, and relied heavily on economic principles throughout his work. He believed that one good theory was sufficient for IB studies, and that theory, he maintained, was internalisation theory. He rejected theoretical pluralism, and believed that IB suffered from a surfeit of theories. Alan was a positivist. The test of a good theory was that it led to clear predictions which were corroborated by empirical evidence. Many IB theories, Alan believed, were weak; their proliferation sowed confusion and they needed to be refuted. Alan’s interpretation of internalisation was, however, unconventional in some respects. He played down the trade-offs presented in Coase’s original work, and substituted heuristics in their place. Instead of analysing internalisation as a context-specific choice between alternative contractual arrangements, he presented it as a strategic imperative for firms possessing strong knowledge advantages. His heuristics did not apply to every possible case, but in Alan’s view they applied in the great majority of cases and were therefore a basis for management action.

Food geographies I: relational foodscapes and the busy-ness of being more-than-food

The study of foodscapes has spread throughout geography at the same time as food scholarship has spearheaded post-disciplinary research. This report argues that geographers have taken to post-disciplinarity to explore the ways that food is ‘more-than-food’ through analyses of the visceral nature of eating and politics and the vital (re)materializations of food’s cultural geographies. Visceral food geographies illuminate what I call the ‘contingent relationalities’ of food in the critical evaluation of the indeterminate, situated politics of ‘feeling food’ and those of the embodied collectivities of obesity. Questions remain, however, about how a visceral framework might be deployed for broader critiques within foodscapes and the study of human geography. The study of food’s vital materialisms opens up investigation into the practices of the ‘makings’ of meat, food waste and eating networks. Analysis of affect, embodiment and cultural practices is central to these theorizations and suggests consideration of the multiple materialisms of food, space and eating. There is, I contend, in the more radical, ‘post-relational’ approaches to food, the need for a note of caution. Exuberant claims for the ontological, vital agency of food should be tempered by, or at least run parallel to, critical questions of the real politik of political and practical agency in light of recent struggles over austerity, food poverty and food justice.

'More-than-human’ resilience(s)? Enhancing community in Finnish forest farms

Community resilience is widely understood as a critical element in the relatively under-explored concept of social resilience. Through engaging with ‘more-than-human’ literatures, a more expansive view of the ‘social’ emerges, which repositions individuals as networked and agency as relational. This moves resilience away from its hegemonic positioning as a neoliberal strategy of individualisation and responsibilisation, with it instead emerging as an everyday ‘doing’ embedded in the human and non-human networks of relationality that we form and are formed by. The paper develops this socio-cultural conceptualisation through an original and empirically grounded discussion of Finnish farm communities and the role of the forest in developing, maintaining and enhancing these essential, connective assemblages. Resilience becomes conceptualised as dynamic, uneven, multiple and contextual performances or resiliences. While this further problematizes the comparative measurement and operationalisation of resilience, its networked and relational nature arguably offers a more inclusive and ethically grounded concept that, furthermore, negates the socio-ecological divide that persists in resilience thinking.

Diastereoselective and enantioselective preparation of nor-mevaldic acid surrogates through desymmetrisation methodology. Enantioselective synthesis of (+) and (-) nor-mevalonic lactones

Solvent-free desymmetrisation of a meso-dialdehyde with chiral alcohols, led to preparation of 4-silyloxy-6-alkyloxytetrahydro-2H-pyran-2-one derivatives with a 96% de. This methodology, which yields the corresponding methyl nor-mevaldates with 99% ee, has been applied to the enantioselective synthesis of the (-)-(R) and (+)-(S) nor-mevalonic acid lactones.

Relational architecture and relational capability: organisational levers to support strategic supplier relationships

The resource based view of strategy suggests that competitiveness in part derives from a firms ability to collaborate with a subset of its supply network to co-create highly valued products and services. This relational capability relies on a foundational intra and inter-organisational architecture, the manifestation of strategic, people, and process decisions facilitating the interface between the firm and its strategic suppliers. Using covariance-based structural equation modelling we examine the relationships between internal and external features of relational architecture, and their relationship with relational capability and relational quality. This is undertaken on data collected by mail survey. We find significant relationships between both internal and external relational architecture and relational capability and between relational capability and relational quality. Novel constructs for internal and external elements of relational architecture are specified to demonstrate their positive influence on relational capability and relationship quality.

Abduction by philosophers: reorienting philosophical methodology

A reorientation is needed in methodological debate about the role of intuitions in philosophy. Methodological debate has lost sight of the reason why it makes sense to focus on questions about intuitions when thinking about the methods or epistemology of philosophy. The problem is an approach to methodology which gives a near exclusive focus to questions about some evidential role that intuitions may or may not play in philosophers' arguments. A new approach is needed. Approaching methodological questions about the role of intuitions in philosophy with an abductive model of philosophical enquiry in mind will help ensure the debate doesn't lose sight of what motivates the debate.

Influence of implant positioning in extraction sockets on osseointegration: histomorphometric analyses in dogs

Aim To evaluate the influence of implant positioning into extraction sockets on osseointegration. Material and methods Implants were installed immediately into extraction sockets in the mandibles of six Labrador dogs. In the control sites, the implants were positioned in the center of the alveolus, while in the test sites, the implants were positioned 0.8 mm deeper and more lingually. After 4 months of healing, the resorptive patterns of the alveolar crest were evaluated histomorphometrically. Results All implants were integrated in mineralized bone, mainly composed of mature lamellar bone. The alveolar crest underwent resorption at the control as well as at the test sites. After 4 months of healing, at the buccal aspects of the control and test sites, the location of the implant rough/smooth limit to the alveolar crest was 2 +/- 0.9 mm and 0.6 +/- 0.9 mm, respectively (P < 0.05). At the lingual aspect, the bony crest was located 0.4 mm apically and 0.2 mm coronally to the implant rough/smooth limit at the control and test sites, respectively (NS). Conclusions From a clinical point of view, implants installed into extraction sockets should be positioned approximately 1 mm deeper than the level of the buccal alveolar crest and in a lingual position in relation to the center of the alveolus in order to reduce or eliminate the exposure above the alveolar crest of the endosseous (rough) portion of the implant. To cite this article:Caneva M, Salata LA, de Souza SS, Baffone G, Lang NP, Botticelli D. Influence of implant positioning in extraction sockets on osseointegration: histomorphometric analyses in dogs.Clin. Oral Impl. Res. 21, 2010; 43-49.

Effect of extrusion on the emulsifying properties of soybean proteins and pectin mixtures modelled by response surface methodology

The objective of this study was to apply response surface methodology to estimate the emulsifying capacity and stability of mixtures containing isolated and textured soybean proteins combined with pectin and to evaluate if the extrusion process affects these interfacial properties. A simplex-centroid design was applied to the model emulsifying activity index (EAI), average droplet size (D-[4.3]) and creaming inhibition (Cl%) of the mixtures. All models were significant and able to explain more than 86% of the variation. The high predictive capacity of the models was also confirmed. The mean values for EAI, D-[4.3] and Cl% observed in all assays were 0.173 +/- 0.015 mn, 19.2 +/- 1.0 mu m and 53.3 +/- 2.6%, respectively. No synergism was observed between the three compounds. This result can be attributed to the low soybean protein solubility at pH 6.2 (<35%). Pectin was the most important variable for improving all responses. The emulsifying capacity of the mixture increased 41% after extrusion. Our results showed that pectin could substitute or improve the emulsifying properties of the soybean proteins and that the extrusion brings additional advantage to interfacial properties of this combination. (C) 2008 Elsevier Ltd. All rights reserved.

Response surface methodology applied to the analysis of rice bran oil extraction process with ethanol

P>Vegetable oils can be extracted using ethanol as solvent. The main goal of this work was to evaluate the ethanol performance on the extraction process of rice bran oil. The influence of process variables, solvent hydration and temperature was evaluated using the response surface methodology, aiming to maximise the soluble substances and gamma-oryzanol transfer and minimise the free fatty acids extraction and the liquid content in the underflow solid. It can be noted that oil solubility in ethanol was highly affected by the water content. The free fatty acids extraction is improved by increasing the moisture content in the solvent. Regarding the gamma-oryzanol, it can be observed that its extraction is affected by temperature when low level of water is added to ethanol. On the other hand, the influence of temperature is minimised with high levels of water in the ethanol.

Study of some physical properties of biodegradable films based on blends of gelatin and poly(vinyl alcohol) using a response-surface methodology

The aim of this work was to study the effect of the hydrolysis degree (HD) and the concentration (C(PVA)) Of two types of poly(vinyl alcohol) (PVA) and of the type (glycerol and sorbitol) and the concentration (C(P)) of plasticizers on some physical properties of biodegradable films based on blends of gelatin and PVA Using a response-surface methodology. The films were prepared with a film forming solutions (FFS) with 2 g of macromolecules (gelatin+PVA)/100 g de FFS. The responses analyzed were the mechanical properties, the solubility, the moisture Content. the color difference and the opacity. The linear model was statistically significant and predictive for puncture force and deformation. elongation at break, solubility in water, Moisture content and opacity. The CPVA affected strongly the elongation at break of the films. The interaction of the HD and the C(P) affected this property. Moreover. the puncture force was affected slightly by the C(PVA). Concerning the Solubility in water, the reduction of the HD increased it and this effect was greater for high CPVA Values. In general. the most important effect observed in the physical properties of the films was that of the plasticizer type and concentration. The PVA hydrolysis degree and concentration have an important effect only for the elongation at break, puncture deformation and solubility in water. (C) 2008 Elsevier B.V. All rights reserved.

Evolutionary fuzzy clustering of relational data

This paper is concerned with the computational efficiency of fuzzy clustering algorithms when the data set to be clustered is described by a proximity matrix only (relational data) and the number of clusters must be automatically estimated from such data. A fuzzy variant of an evolutionary algorithm for relational clustering is derived and compared against two systematic (pseudo-exhaustive) approaches that can also be used to automatically estimate the number of fuzzy clusters in relational data. An extensive collection of experiments involving 18 artificial and two real data sets is reported and analyzed. (C) 2011 Elsevier B.V. All rights reserved.